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Literature summary for 2.1.1.299 extracted from

  • Dong, C.; Dong, G.; Li, L.; Zhu, L.; Tempel, W.; Liu, Y.; Huang, R.; Min, J.
    An asparagine/glycine switch governs product specificity of human N-terminal methyltransferase NTMT2 (2018), Commun. Biol., 1, 183 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.1.1.299

Crystallization (Commentary)

Crystallization (Comment) Organism
purified recombinant NTMT2 in binary complex with S-adenosyl-L-methionine and in ternary complex with S-adenosyl-L-homocysteine and unmethylated substrate peptide SPKRIA, X-ray diffraction structure determination and analysis at 1.20-2.0 A resolution. A methylated alpha-amino group in the N-terminus of the peptide is traced in the crystal structure Homo sapiens

Protein Variants

Protein Variants Comment Organism
N223A site-directed mutagenesis, inactive mutant Homo sapiens
N89G site-directed mutagenesis, the mutant shows profoundly altered catalytic activities and product specificities Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens Q5VVY1
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2 S-adenosyl-L-methionine + PPKRIA mono- and dimethylation by NTMT2 Homo sapiens 2 S-adenosyl-L-homocysteine + ?
-
 ?
3 S-adenosyl-L-methionine + GPKRIA mono-, di-, and trimethylation by NTMT2 Homo sapiens 3 S-adenosyl-L-homocysteine + ?
-
 ?
additional information NTMT2 is a mono-methyltransferase, substrate specificity, overview. But NTMT2 is also able to di-/tri-methylate the GPKRIA peptide and di-methylate the PPKRIA peptide, otherwise it is predominantly a mono-methyltransferase. The residue N89 of NTMT2 serves as a gatekeeper residue that regulates the binding of unmethylated versus mono-methylated substrate peptide.The substrate peptide is deeply inserted into the binding pocket through hydrophilic and hydrophobic interactions, and the alpha-amine of the first residue (S1) points towards the sulfur atom of SAH. In the NTMT2 complex, S1 fits snugly into the channel, where the main-chain O atom is anchored by N223 in NTMT2 (N168 in NTMT1, EC 2.1.1.244) through hydrogen bonding. No activity with peptides TPKRIA, VPKRIA, IPKRIA, DPKRIA, EPKRIA, NPKRIA, and QPKRIA Homo sapiens ?
-
-
S-adenosyl-L-methionine + APKRIA monomethylation by NTMT2 Homo sapiens S-adenosyl-L-homocysteine + ?
-
 ?
S-adenosyl-L-methionine + CPKRIA monomethylation by NTMT2 Homo sapiens S-adenosyl-L-homocysteine + ?
-
 ?
S-adenosyl-L-methionine + FPKRIA monomethylation by NTMT2 Homo sapiens S-adenosyl-L-homocysteine + ?
-
 ?
S-adenosyl-L-methionine + HPKRIA monomethylation by NTMT2 Homo sapiens S-adenosyl-L-homocysteine + ?
-
 ?
S-adenosyl-L-methionine + KPKRIA monomethylation by NTMT2, very low activity Homo sapiens S-adenosyl-L-homocysteine + ?
-
 ?
S-adenosyl-L-methionine + LPKRIA monomethylation by NTMT2, very low activity Homo sapiens S-adenosyl-L-homocysteine + ?
-
 ?
S-adenosyl-L-methionine + MPKRIA monomethylation by NTMT2 Homo sapiens S-adenosyl-L-homocysteine + ?
-
 ?
S-adenosyl-L-methionine + RCC1
-
 Homo sapiens S-adenosyl-L-homocysteine + ?
-
 ?
S-adenosyl-L-methionine + RPKRIA monomethylation by NTMT2 Homo sapiens S-adenosyl-L-homocysteine + ?
-
 ?
S-adenosyl-L-methionine + SPKRIA binding structure of SAM/SAH and of the substrate peptide, overview. SPKRIA peptide is derived from N-terminus of RCC1 protein. NTMT2, unlike NTMT1 (EC 2.1.1.244), fails to di-/tri-methylate SPKRIA Homo sapiens S-adenosyl-L-homocysteine + ?
-
 ?
S-adenosyl-L-methionine + WPKRIA monomethylation by NTMT2 Homo sapiens S-adenosyl-L-homocysteine + ?
-
 ?
S-adenosyl-L-methionine + YPKRIA monomethylation by NTMT2 Homo sapiens S-adenosyl-L-homocysteine + ?
-
 ?

Subunits

Subunits Comment Organism
More based on the folding pattern, NTMT2 is a SAM-dependent class I methyltransferase, which consists of a central seven-stranded beta-sheet (beta1-beta5 and beta8-beta9), flanked by three alpha-helices (alpha3-alpha5) and two alpha-helices (alpha6-alpha7) on each side, respectively. In addition, NTMT2 contains two auxiliary regions: an N-terminal alpha-lid (nu1, alpha1-alpha2), and a beta-lid (beta6-beta7) inserted between beta5 and alpha8. These two lids cover the core domain that contributes to the substrate recognition Homo sapiens

Synonyms

Synonyms Comment Organism
alpha-N-terminal methyltransferase 2
-
 Homo sapiens
N-terminal methyltransferase
-
 Homo sapiens
NTMT2
-
 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
S-adenosyl-L-methionine dependent on, binding structure of SAM/SAH, overview Homo sapiens

General Information

General Information Comment Organism
evolution structural comparison of isozymes NTMT1 and NTMT2, structural alignment of NTMT1 (PDB ID 5E1B) and NTMT2, overview. NTMT1 and NTMT2 employ a similar substrate recognition mode. NTMT2 is a SAM-dependent class I methyltransferase Homo sapiens
additional information substrate and ligand binding structures of NTMT1 (EC 2.1.1.244) and NTMT2, and proposed catalytic mechanism of NTMT2, overview Homo sapiens
physiological function protein methylation participates in regulation of a broad spectrum of cellular processes. Besides the extensively studied protein lysine/arginine methylation, the addition of a methyl group at the free alpha-N-termini of proteins represents a unique mode of post-translational modification Homo sapiens